With the goal of obtaining derivatives of the potent antileukemic, antiviral, and immunosuppressive nucleoside, 1-0-D-arabinofuranosylcytosine (cytarabine, ara-C), possessing superior therapeutic properties, a series of 5'-esters have been synthesized. In our earlier work the 5'-0-trityl• ether of ara-C was converted into its N4trichloroethoxycarbonyl (TCEC) derivative, and after detritylation, the A'4-TCEC compound was acylated at the 5' position. The resultant iV4-TCEC 5'-ester was treated with Zn dust to obtain the desired 5'-ester. Yields were 3-5%. In our later syntheses, a greatly simplified synthetic route was employed which utilized protonation for protection of the iV4-amino group. Thus, ara-C-HC1 was acylated at the 5' position with an acid chloride, and the resultant 5'-ester• HC1 was converted to the free base. Yields were 40-80%. This method should have general application for the synthesis of 5'-esters of nucleosides bearing reactive amino groups. A variety of aromatic and aliphatic carboxylate and sulfonate esters have been prepared. Of these, the palmitoyl, benzoyl, p-methoxybenzoyl, and 1-adamantoyl esters showed marked superiority as immunosuppressive and antileukemic agents compared to the parent compound when administered as a single dose in the mouse.The 5'-ester of l-/3-D-arabmofuranosylcytosine2,8 (cytosine arabinoside, cytarabine, aiacytidine, ara-C) with adamant ane-l-carboxy lie acid (5'-adamantoyl ara-C), first synthesized by Neil, et al.,4 has been shown to possess superior therapeutic properties (compared to ara-C) in the treatment of L1210 leukemic mice4 and to possess greater immunosuppressive activity in this species5 and in the rat.6,7 Furthermore, in contrast to the parent compound, which exhibits short duration of action, 5'-adamantoyl ara-C possesses long-lasting